3-Acetyl-4-hydroxybenzonitrile -Drug Synthesis Database

【结构式】

【分子编号】12857

【品名】3-Acetyl-4-hydroxybenzonitrile

【CA登记号】

【分子式】C₉H₇NO₂

【分子量】161.16012

【元素组成】C 67.08% H 4.38% N 8.69% O 19.86%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The cyclization of 3-acetyl-4-hydroxybenzonitrile (I) with acetone by means of pyrrolidine in toluene gives 2,2-dimethyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (II), which is reduced with NaBH4 yielding the corresponding alcohol (III). The dehydration of (III) with p-toluenesulfonic acid in refluxing toluene affords 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (IV), which is treated with m-chloroperbenzoic acid (MCPBA) to give the corresponding epoxide (V) . The condensation of (V) with pyridin-2(1H)-one (VI) by means of pyridine or benzyl trimethylammonium hydroxide (2) in refluxing ethanol yields trans-3-hydroxy-2,2-dimethyl-4-(2-oxo-1,2-dihydropyridin-1-yl)-3,4-dihydro-2H-1-benzopyran-6-carbonitrile (VII), which is finally dehydrated with NaOH in refluxing dioxane , or with NaH in refluxing THF. When the condensation of epoxide (V) with pyridone (VI) is carried out with NaH in DMSO mixtures of the intermediate (VII) and the final compound bimakalim are obtained; these compounds are easily separated.

参考文献中间体

合成目标

【1】 Robinson, C.; Robinson, K.A.; Castaner, J.; Bimakalim. Drugs Fut 1996, 21, 4, 351.
【2】 Hausler, G.; Gericke, R.; Wurziger, H.; Baumgarth, M.; Lues, I.; De Peyer, J.; Bergmann, R. (Merck Patent GmbH); Chroman derivs. AU 8782689; DE 3726261; EP 0273262; JP 1988170376 .
【3】 Garcia, G.; Di Malta, a.; Gautier, P. (Sanofi-Synthelabo ); 2,2-Dimethylchromene derivs., preparation process and pharmaceutical compsns. containing them. AU 8823660; EP 0312432; EP 0556872; FR 2621587; JP 1990000180 .
【4】 Hausler, G.; Gericke, R.; Wurziger, H.; Baumgarth, M.; Lues, I.; Bergmann, R.; De Peyer, J. (Merck Patent GmbH); Chroman derivs. AU 8936440; DE 3820506; EP 0346724; JP 1990040375; US 5387587 .
【5】 Bergmann, R.; Gericke, R.; Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new channel activators. J Med Chem 1990, 33, 2, 492-504.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	12857	3-Acetyl-4-hydroxybenzonitrile		C₉H₇NO₂	详情	详情
(II)	12858	2,2-Dimethyl-4-oxo-6-chromanecarbonitrile		C₁₂H₁₁NO₂	详情	详情
(III)	12859	4-Hydroxy-2,2-dimethyl-6-chromanecarbonitrile		C₁₂H₁₃NO₂	详情	详情
(IV)	12860	2,2-Dimethyl-2H-chromene-6-carbonitrile		C₁₂H₁₁NO	详情	详情
(V)	12861	2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile		C₁₂H₁₁NO₂	详情	详情
(VI)	12862	2(1H)-Pyridinone	142-08-5	C₅H₅NO	详情	详情
(VII)	12863	(3S,4R)-3-Hydroxy-2,2-dimethyl-4-[2-oxo-1(2H)-pyridinyl]-3,4-dihydro-2H-chromene-6-carbonitrile		C₁₇H₁₆N₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

By condensation of 4-(2-quinolinylmethoxy)benzaldeyde (I) with 2-hydroxy-5(1H-tetrazol-5-yl)acetophenone (II) by means of KOH in ethanol/water. The intermediates (I) and (II) have been obtained as follows: Benzaldehyde (I): By condensation of 2-(chloromethyl)quinoline (III) with 4-hydroxybenzaldehyde (IV) by means of K2CO3 in hot DMF. Acetophenone (II): The acetylation of 4-hydroxybenzonitrile (V) with acetic anhydride/sulfuric acid and AlCl3 gives 5-cyano-2-hydroxyacetophenone (VI), which is then cyclized with sodium azide and ammonium chloride in hot DMF.

参考文献中间体

合成目标

【1】 Zwaagstra, M.E.; et al.; Synthesis and structure - activity relationships of carboxylated chalcones: A novel series of CysLT1 (LTD4) receptor antagonists. J Med Chem 1997, 40, 7, 1075.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	25883	4-(2-quinolinylmethoxy)benzaldehyde		C₁₇H₁₃NO₂	详情	详情
(II)	25884	1-[2-hydroxy-5-(1H-1,2,3,4-tetraazol-5-yl)phenyl]-1-ethanone		C₉H₈N₄O₂	详情	详情
(III)	13162	2-(Chloromethyl)quinoline; alpha-Chloroquinaldine	4377-41-7	C₁₀H₈ClN	详情	详情
(IV)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(V)	25109	4-hydroxybenzonitrile	767-00-0	C₇H₅NO	详情	详情
(VI)	12857	3-Acetyl-4-hydroxybenzonitrile		C₉H₇NO₂	详情	详情

Extended Information